Conventionally, as a method of analyzing a liquid collected from a living organism or the like, an analyzing method is known that uses an analyzing device in which a liquid channel is formed. The analyzing device is capable of controlling a fluid using a rotating apparatus. Since the analyzing device is capable of performing dilution of a sample liquid, solution measurement, separation of solid components, transfer and distribution of a separated fluid, mixing of a solution and a reagent, and the like by utilizing centrifugal force, various biochemical analyses can be carried out.
An analyzing device 50 described in Patent Document 1 which transfers a solution using centrifugal force is arranged as illustrated in FIG. 107 such that after injecting a sample liquid into a measuring chamber 52 from an inlet 51 with an insertion tool such as a pipette and holding the sample liquid by a capillary force of the measuring chamber 52, the sample liquid is transferred to a separating chamber 53 by a rotation of the analyzing device. By providing such an analyzing device which uses a centrifugal force as a power source for liquid transfer with a disk-like shape, microchannels for performing liquid transfer control can be arranged radially. Since no wasted area is created, the disk-like shape is used as a favorable shape.
In addition, as illustrated in FIG. 108A, an analyzing device 54 described in Patent Document 2 is arranged so as to collect a sample liquid by a capillary action from an inlet 55 to fill a first cavity 56 and transfer the sample liquid in the first cavity 56 to a separation cavity 58 by a rotation of the analyzing device 54 around an axial center 57. Since a sample liquid can be directly collected from the inlet 55, there is an advantage that the sample liquid can be injected into the analyzing device by a simple operation that does not require an insertion tool such as a pipette.
Conventionally, analyzing apparatuses which use an analyzing device that internally collects a sample liquid and which analyze characteristics of the sample liquid while rotating the analyzing device around the axial center of the same have been put to practical use.
In recent years, there has been an increase in market demands for reductions in sample liquid volume, downsizing of apparatuses, short-time measurement, simultaneous multiple measurement, and the like. An analyzing apparatus with higher accuracy is desired which is capable of causing a reaction between a sample liquid such as blood and various analytical reagents, detecting a mixture of the sample liquid and the reagent, and testing stages of progression of various diseases within a short period of time.
FIG. 109 illustrates an analyzing device according to Patent Document 3 which includes a capillary measurement segment and a hydrophilic stopper.
The analyzing device is made up of air ducts V1, V2, V3, and V4 which communicate with the atmosphere, sample reservoirs R1, R2, and R3, a measurement segment L formed by a capillary, and a hydrophilic stopper S1.
The measurement segment L ensures that an accurate amount of a liquid sample is to be measured and distributed for the purpose of improving analytical precision. A liquid sample injected into the sample reservoir R1 flows into the measurement segment L from the sample reservoir R1 by a capillary force and fills the U-shaped measurement segment L.
Both ends of the measurement segment L communicate with the atmosphere via the air ducts V1 and V2. The sample liquid is moved by a capillary force to the hydrophilic stopper S1, but stops at a connected section of the measurement segment L and the hydrophilic stopper S1.
This is because a configuration in which the width of the hydrophilic stopper S1 is broader than the width of the measurement segment L prevents the liquid sample from coming into contact with a wall face of the hydrophilic stopper S1 and consequently halting the capillary force.
When the analyzing device is set on a rotary platform and is rotated at sufficient speed to overcome the resistance of the hydrophilic stopper S1, the liquid contained in the measurement segment L passes the stopper S1 and enters the sample reservoir R2 by a centrifugal force and a capillary force. When the sample liquid passes the hydrophilic stopper S1 due to a centrifugal force, air enters from the air ducts V1 and V2, consequently determining a length of a liquid column of the measurement segment L and, in turn, a sample amount to be sent to the sample reservoir R2.
A further sample reservoir R3 is provided underneath the sample reservoir R2, which can be used to cause a reaction with the sample liquid or to prepare the sample liquid for subsequent analysis. A liquid injected in the sample reservoir R2 is transported from the sample reservoir R2 to the sample reservoir R3 by a centrifugal force.
Conventionally, there are methods of electrochemically or optically analyzing a biological fluid using an analyzing device in which a microchannel is formed. Methods of electrochemical analysis include, as a biosensor that analyzes a specific component in a sample liquid, determining a blood glucose level or the like by measuring a current value obtained by a reaction between blood glucose and a reagent such as glucose oxidase held in a sensor.
In addition, with an analyzing method using an analyzing device, fluid control can be realized using a rotating apparatus having a horizontal axis, and sample liquid measurement, separation of cytoplasmic material, transfer and distribution of separated fluids, mixing/agitation of liquids and the like can be performed utilizing a centrifugal force. Therefore, various biochemical analyses can be carried out.
Conventional methods of collecting a sample liquid for introducing a sample into an analyzing device include an electrochemical biosensor illustrated in FIG. 110.
The electrochemical biosensor is formed by bonding an insulated substrate 225 to a cover 226 with a spacer 227 and a reagent layer 228 sandwiched in-between. A sample liquid is introduced into a cavity 230 by a capillary action through a suction port 229 on the cover 226. The sample liquid is guided to the positions of an action pole 231 and an antipole 232 on the insulated substrate 225 and the reagent layer 228. Reference numeral 233 denotes an air relief hole.
In this case, a quantitative collection of the sample is performed by a cubic capacity of the cavity 230. The current value created by a reaction between the sample liquid and the reagent at the action pole 231 and the antipole 232 is connected to and read by an external measurement apparatus, not shown, via leads 234 and 235 (for example, refer to Patent Document 4).
Furthermore, with a centrifugal transfer biosensor illustrated in FIG. 108B, a sample liquid is quantitatively collected into a first capillary cavity 312 by a capillary action from an inlet port 313. By subsequently causing a centrifugal force to act, the sample liquid in the capillary cavity 312 is transferred to a receiving cavity 317 via a filtering material 315, a first channel 314, a second cavity 316, and a core 318. The sample liquid involved in a reaction with a reagent in the receiving cavity 317 is centrifugally separated. Only a solution component is collected by a capillary force into the second cavity 316 and a reaction state is optically read (for example, refer to Patent Document 2).
Moreover, with a centrifugal transfer biosensor 400 illustrated in FIG. 111, a sample is transferred from an inlet port 409 to an outlet port 410 by a capillary force through a serpentine continuous microconduit 411. After filling respective capillary cavities 404a to 404f with the sample liquid, the sample liquid in the respective capillary cavities are distributed at positions of respective ventilation holes 406a to 406g by a centrifugal force generated by a rotation of the biosensor. The sample liquid is then transferred to a next processing chamber (not shown) through respective coupling microconduits 407a to 407f (for example, refer to Patent Document 5). Reference characters 408a to 408f denote valve function sections.
Patent Document 1: National Publication of International Patent Application No. 1995-500910
Patent Document 2: National Publication of International Patent Application No. 1992-504758
Patent Document 3: National Publication of International Patent Application No. 2005-518531
Patent Document 4: Japanese Patent Laid-Open No. 2001-159618
Patent Document 5: National Publication of International Patent Application No. 2004-529333